Recombinant human acid ??-glucosidase enzyme therapy for infantile glycogen storage disease type II: Results of a phase I/II clinical trial

Abstract

This phase I/II first study of recombinant human GAA derived from CHO cells showed that rhGAA is capable of improving cardiac and skeletal muscle functions in infantile GSD-II patients. Further study will be needed to assess the overall potential of this therapy.

Improved efficacy of gene therapy approaches for Pompe disease using a new, immune-deficient GSD-II mouse model

“…10 Long-term correction of GSD-II in GAA-KO/SCID mice F Xu et al GSD-II patients. 15,20 Recently, it has been demonstrated that restoration of a single muscle's contractile force can be achieved after intramuscular injection of an AAV vector encoding hGAA. 21 However, the evaluation of overall gross muscle strength has not been reported after attempting gene therapy using viral vectors in GSD-II animal models.…”

“…11 Similarly, in our previous studies of ERT in humans, the onset of anti-rhGAA antibodies have also been correlated with the lack of sustained skeletal muscle efficacy. 15 To both circumvent and prove that production of antihGAA antibodies is a significant problem potentially limiting the efficacy of both ERT or gene therapy approaches to the treatment of GSD-II, we have now developed a new, immune-deficient mouse model of GSD-II. This was achieved by interbreeding GAA-KO mice with severe combined immune-deficient (SCID) mice, generating double knockout, GAA-KO/SCID mice.…”

CRIM‐negative infantile Pompe disease: 42‐month treatment outcome

“…In addition, it was hypothesized from the first clinical trials that the presence or absence of cross-reactive immunological material (CRIM) may affect prognosis (Amalfitano et al 2001). CRIM-negative patients are completely unable to form any precursor form of native enzyme, whereas patients who are able to produce some precursor form of abnormalor normal-size native enzyme are CRIM-positive.…”

Stbd1 is highly elevated in skeletal muscle of Pompe disease mice but suppression of its expression does not affect lysosomal glycogen accumulation

“…Patients with the most severe infantile form normally die within the first year of life, while in the milder late-onset forms, muscle weakness is the primary symptom and respiratory failure is the major cause of significant morbidity and mortality [1]. Enzyme replacement therapy (ERT) with recombinant human GAA (rhGAA, alglucosidase alfa) is currently the only available therapy for Pompe disease with remarkable success, but also with significant limitations including the high cost for life-long administration of high-dose enzyme, poor clinical outcomes caused by the formation of high-titer anti-rhGAA antibodies in the majority of patients, and reduced efficacy in the skeletal muscle [2][3][4][5]. Thus, there is an unmet need to develop improved therapies for Pompe disease.…”